Cardiovascular disease is a major cause of death and disability in the United States and in general in western civilizations, with the predominant etiology (i.e., the set of factors that contributes to the occurrence of a disease, considered the cause of a disease or abnormal condition) related to atherosclerosis. In regards to atherosclerosis, the site of the pathogenesis is primarily the arterial wall or wall of the blood vessel. Localized forms of the atherosclerotic disease, such as the deposit of plaque on the walls of blood vessels, can restrict local blood flow and require surgical intervention.
X-ray angiography wherein blood vessels are injected with a radio-opaque dye that outlines them on x-ray images, displays the passageway though the blood vessel (i.e., vessel lumen). While X-ray angiography is effective in detecting the luminal narrowing caused by plaque, this technique does not provide information regarding the nature, structure, or vulnerability to rupture of the processes that underlie vessel narrowing. More specifically, other than obtaining lumenographic measures, the vessel wall cannot be visualized and the atherosclerotic plaques cannot be characterized using X-ray angiography.
In this regard, anatomically the wall of an artery or blood vessel consists of three layers, the innermost consisting of an inner surface of smooth endothelium covered by a surface of elastic tissues: the two form the tunica intima. The tunica media, or middle coat, is thicker in arteries, particularly in the large arteries, and consists of smooth muscle cells intermingled with elastic fibers, where the muscle-cell and elastic fibers circle the vessel. The outer layer, the tunica adventitia, is the strongest of the three layers and is composed of collagenous and elastic fibers. The tunica adventitia provides a limiting barrier, protecting the vessel from overexpansion.
Also, therapeutic methods, such as intravascular intervention, may experience failure due to the lack of sufficiently precise imaging methods. An imaging system capable of providing detailed, qualitative and quantitative data regarding the status of vascular walls at the time of surgical intervention, could greatly improve efficacy by enabling the selection of the intervention method to be customized to the particular need. It also would serve to provide precise guidance for various forms of localized therapy.
In a limited number of applications, intravascular ultrasound (IVUS) is used to acquire images of the atherosclerotic plaques. J. R. Spears, H. J. Marais, J. Serur, O. Pomerantzelff, R. P. Geyer, R. S. Sipzener, R. Weintraub, R. Thurer, “In vivo coronary angioscopy,” J. Am. Coll. Cardiol., 1, 1311-1314 (1983). The resulting images, however, have several drawbacks, including the relative insensitivity to soft tissue and the inability to reliably detect and discriminate thrombus (new or organized) superimposed upon plaque from soft lipid-laden plaques, particularly in the presence of calcifications which are a common feature of the disease. Also, the presence of artifacts related to transducer angle relative to the vessel wall, and an imaging plane limited to the aperture of the transducer in variable resolution at different depths of view are further problems with this approach.
The feasibility of identifying atherosclerotic lesions by employing magnetic resonance (MR) microimaging in vitro has previously been suggested. See, for example, Pearlman et al., “Nuclear Magnetic Resonance Microscopy of Atheroma in Human Coronary Arteries,” Angiology, Vol. 42, pp. 726-33 (1991); Asdente et al., “Evaluation of Atherosclerotic Lesions Using NMR Microimaging,” Atherosclerosis, Vol. 80, pp. 243-53 (1990); and Merickel et al., “Identification and 3-d Quantification of Atherosclerosis Using Magnetic Resonance Imaging,” Comput. Biol. Med., Vol. 18, pp. 89-102 (1988). It has also been demonstrated that MRI can potentially be used for quantification of atherosclerosis, for planning and targeting RF ablation therapies for cardiac arrhythmias, for MRI-guided coronary catheterization procedures, and even intravascular gene therapy. See, generally, Merickel et al., “Noninvasive Quantitative Evaluation of Atherosclerosis Using MRI and Image Analysis,” Arteriosclerosis and Thrombosis, Vol. 13, pp. 1180-86 (1993); “Visualization and Temporal/Spatial Characterization of Cardiac Radiofrequency Ablation Lesions Using Magnetic Resonance Imaging” Lardo et al, Circulation. 2000; 102:698-705; “Real-Time Magnetic Resonance Imaging-Guided Coronary Catheterization in Swine” by Omary et al, Circulation 2003; 107:2656-2659; and “Magnetic Resonance Imaging Permits In Vivo Monitoring of Catheter-Based Vascular Gene Delivery” by Yang et al, Circulation. 2001; 104:1588-1590.
In addition to identification and the potential of MRI-guided intervention of atherosclerotic lesions, the vasculature can offer practical and/or minimally-invasive access via diagnostic and therapeutic catheters, needles, and other interventional devices, to cancerous and other lesions, to sites of injury or congenital abnormalities. These are areas where devices employing MR micro-imaging can potentially be of major benefit to disease diagnosis and intervention, by providing sub-millimeter resolution of pathologic tissues for biopsy, morphologic or functional MRI analysis, and precision guidance and delivery of therapy. Specific areas of potential value include brain tumors, arterio-venous malformations, aneurysms, tumors of the liver and pancreas, and congenital abnormalities.
Conventional clinical endoscopy permits the routine identification of, and minimally-invasive intervention for, suspect lesions in the gastro-intestinal tract, the bladder and other body cavities, as well as the guidance of laparoscopic procedures. It is responsible for identifying hundreds-of-thousands of new cancer cases in the USA annually [American Cancer Society; Cancer Facts and Figures 2007. Atlanta: American Cancer Society; 2007. http://www.cancer.org/downloads/STT/CAFF2007PWSecured.pdf]. Current endoscopy procedures are performed with imaging modalities including the optical endoscope, optical coherence tomography (OCT) and IVUS. A difference between current MR micro-imaging approaches and existing IVUS, OCT, and optical endoscopy, is that the latter provide internal high-resolution examination directly from the viewpoint of the probe. On the other hand, existing intravascular MRI (IVMRI) cannot presently do this directly because localization depends entirely on the fixed external localizing MRI gradient coils and hence is intrinsically locked to the laboratory frame-of-reference (FoR) of the MRI scanner.
Further opportunities also exist for internal MR micro-imaging outside the vasculature, analogous to those applications currently served by conventional optical endoscopy. These include but are not limited to trans-esophageal MRI (see “Transesophageal Magnetic Resonance Imaging” by Shunk et al, Magn. Reson. Med 1999; 41:722-726), which can be used, for example, to visualize aortic lesions beyond the esophageal track which cannot be done by visual endoscopy (see “Statin-Induced Cholesterol Lowering and Plaque Regression After 6 Months of Magnetic Resonance Imaging-Monitored Therapy”, Lima et al, Circulation. 2004; 110:2336-2341); transurethral MRI for investigating incontinence, disorders of the urinary tract, and bladder cancer (see “Endourethral MRI”, Quick et al, Magnetic Resonance in Medicine 2001; 45:138-146); endorectal MRI for prostate cancer (see “Phased-Array MRI of Canine Prostate Using Endorectal and Endourethral Coils”, Young et al, Magnetic Resonance in Medicine 2003; 49:710-715), and its extension to colon cancer. Indeed applications are not limited to blood vessels or body cavities or flexible devices as MR micro-imaging is practical with needle devices incorporating MRI antenna, for example, for performing MR-guided needle biopsies of tumors and/or treating them with hypo- or hyper-thermic therapy under MRI guidance; or indeed use of rigid cannula probes, to guide and locate electrodes under MRI-guidance to provide deep brain stimulation (DBS) as a treatment for Parkinson's disease (see “An Active Microelectrode System for Experimental MRI-Guided Intracranial Intervention”, Karmarkar et al, Proc. Intl. Soc. Mag. Reson. Med. 2005; 13: 2162).
As is known to those skilled in the art, in a general sense MRI involves providing bursts of radio frequency (RF) energy on a specimen positioned within a main magnetic field in order to induce responsive emission of magnetic radiation from the hydrogen nuclei or other nuclei. The emitted signal can be detected in such a manner as to provide information as to the intensity of the response and the spatial origin of the nuclei emitting the responsive magnetic resonance signal. In general, imaging can be performed in a slice or plane, in multiple planes, or in a three-dimensional (3D) volume with information corresponding to the responsively emitted magnetic radiation being received by a computer which stores the information in the form of numbers corresponding to the intensity of the signal. The pixel value can be established in the computer using applications programs that embody any one of a number of mathematical processing techniques (e.g., typically Fourier Transformation, FT) which converts the signal amplitude as a function of time to signal amplitude as a function of frequency or spatial coordinates. The signals may be stored in the computer and may be delivered with or without enhancement to a display (e.g., CRT, LCD, plasma screen display, digital light projector). The image created from or by the computer output is presented through monochrome presentations with varying in intensity (e.g., gray scale presentation) or through color presentations with varying in hue and intensity. See also for example U.S. Pat. No. 4,766,381.
Yuan et al., “Techniques for High-Resolution MR Imaging of Atherosclerotic Plaques,” J. Magnetic Resonance Imaging, Vol. 4, pp. 43-49 (1994) discloses a fast spin echo MR imaging technique to image atherosclerotic plaques on an isolated vessel that has been removed by carotid endarterectomy. It has also been suggested that the fat content of atherosclerotic plaque in excised tissue samples can be determined using chemical shift imaging or chemical shift spectroscopy. See, generally, Vinitski et al., “Magnetic Resonance Chemical Shift Imaging and Spectroscopy of Atherosclerotic Plaque,” Investigative Radiology, Vol. 26, pp. 703-14 (1991); Maynor et al., “Chemical Shift Imaging of Atherosclerosis at 7.0 Tesla,” Investigative Radiology, Vol. 24, pp. 52-60 (1989); and Mohiaddin et al., “Chemical Shift Magnetic Resonance Imaging of Human Atheroma,” Br. Heart J., Vol. 62, pp. 81-89 (1989).
The foregoing non-patent articles in the aggregate could lead one skilled in the art to conclude that MR, while having potential for fully characterizing vessel wall disease, suffers from low anatomic resolution unless used in vitro on small specimens with high resolution methods. Also, while MRI techniques should make it possible to distinguish between the three layers of the vessel wall and detect atherosclerotic lesions (even before they calcify), the signal-to-noise-ratio (SNR) that is obtained when using standard receiver coils (e.g., surface or local coils) is presently not sufficiently high for the desired resolution. In some of these MRI techniques, a small receiver probe or coil is introduced into a blood vessel such as by means of a catheter which is then utilized to image the arterial wall. Most of these coils or probes have a size and mechanical design constraints that do not allow them to be used to image small blood vessels.
There has been described a intravascular catheter antenna design (e.g., a loopless antenna design) that can be made very thin and whose electromagnetic (EM) properties are virtually independent of its diameter. It also has been reported that this antenna design provides useful SNR in a cylindrical volume around the catheter. Ocali O, Atalar E, “Intravascular Magnetic Resonance Using a Loopless Catheter Antenna”, Magnetic Resonance in Medicine 37, 112-118 (1997).
There also is described in U.S. Pat. No. 5,928,145 (the teachings of which are incorporated herein by reference), methods for MRI and spectroscopic (MRS) analysis as well as a corresponding apparatus and magnetic resonance antenna assembly. Such imaging methods include positioning a specimen within a main magnetic field and introducing an antenna having a loopless antenna portion in close proximity to the specimen. RF pulses are provided to the region of interest to excite MR signals, gradient magnetic pulses are applied to the region of interest with the antenna receiving MR signals and emitting excitation signals. A processor processes the responsive output signals to provide image information for display in a desired manner. In a preferred use the antenna having a loopless antenna portion is introduced into small blood vessels of a patient to facilitate determination of atherosclerotic plaque.
While existing internal clinical imaging devices such as endoscopes and IVUS, provide internal high-resolution examination directly from the viewpoint of the inserted probe, in conventional MRI (including that done using the loopless antenna) the image FoR is locked to the coordinate system of the MRI scanner (i.e., the scanner coordinate system). This means that imaging from the viewpoint of an introduced internal MRI antenna or probe cannot be done without performing an interrogation to determine the probe's location in the scanner frame, followed by feedback and computation of new position coordinates to feed to the system's external gradient coils, before local MRI from the probe's viewpoint can be done. This process is inefficient in imaging time where real-time imaging from the site of the probe is required, and also costs valuable signal-to-noise ratio (SNR) when the time spent locating the signals could be better spent on signal averaging to improve SNR. Additionally RF power deposition from MRI pulses applied by the body coil is a significant issue with internal antenna probes, due to coupling of the fields induced in the large volume of the body, with the internal probe. In some cases as described for example, in U.S. Pat. No. 5,928,145, data for multiple slices can be acquired while the antenna or probe is maintained fixed at a single location within the specimen or body.
It thus would be desirable to provide new systems, signal detection devices and methods for MRI in which the FoR is not locked to the scanner or its coordinate system but rather is locked to a small MRI probe or signal detection device analogous to an endoscope. It would be particularly desirable to provide such devices and methods that would allow the feed-back/interrogation process associated with conventional MRI techniques and devices to be eliminated. It also would be particularly desirable to provide such methods and devices that also would restrict RF excitation to the small volume over the probe itself. Such detection devices preferably would be simple in construction and such methods would not require development of skills above and beyond those normally exercised by those of ordinary skill in the art.